Preventive programs have been offered for various cancers since the middle of the fifties. For certain cancers even population wide screening programs exist in various developed countries. Such screening programs are applicable for cancer entities and the respective precursor stages such as e.g. cervical cancer, cancers of the urinary system, of the respiratory tract and others.
In all cases of cancer screening the outcome of a diagnostic test is categorized in accordance with the severity of the detected lesion. Grading systems for categorizing cancers of different origins have been established and are widely used. In general for any cancer type low grade tumors can be found that are either benign or are mostly benign with a certain risk for progression to malignant growth.
Generally the detection of low grade lesions imposes problems to the diagnosing physician and on the patient. A moderate to high percentage of low grade lesions has the tendency to regress spontaneously without any further treatment necessary. On the other hand there is also a lower percentage of low grade lesions that will progress to more severe forms and will end up as invasive cancer. The dilemma with low grade lesions in practice is that it is hard to predict which particular lesion is prone to regress and which will progress to invasive cancer.
Several attempts have been made to predict the risk for progression and the potential for aggressive growth of low grade lesions. Especially molecular markers have been examined that might have the potential to predict progression. Especially the expression level of cell cycle regulation proteins has been checked and has been found to be helpful under certain circumstances.
Despite all attempts made so far there is a strong need for methods that allow predict the progression risk for tumors and especially for low grade cancerous lesions and cancer precursor lesions. Therefore, it is the object of the present invention to provide a method of predicting the progression risk of tumors.
The inventor found that detection of overexpression of cyclin-dependent kinase inhibitors may be used to predict the progression risk of tumors and also of early cancer precursor lesions. In addition the detection of a combination of cyclin-dependent kinase inhibitors and of cell proliferation markers may be used for prediction of the progression risk of tumors.